We propose that the Adh-gene-enzyme system be used to study the mechanism of action of chemical mutagens in a higher organism. This system is unique for this purpose because (1) chemical methods have been developed to detect forward mutations, (2) chemical procedures have been developed to detect reverse mutations, and (3) the product of the gene, alcohol dehydrogenase (ADH) has been purified and chemically characterized, and will soon be sequenced. This proposal involves 4 separate steps: 1. We will generate Adh-negative mutants with five interesting chemical mutagens. 2. We will characterize these mutants with regard to whether they yield ADH-like cross-reacting material (CRM). 3. For those mutants that are CRM-negative, we will carry out reversion analysis and examine their polytene chromosomes. The data generated from these experiments will yield important information concerning 1) the mutation rate of a given mutagen at a well defined locus, 2) the rate at which CRM-positive mutants are generated relative to the total rate, and 3) the changes at the nucleotide level which the particular mutagen generates.